Assessing Lung Cancer Screening Programs under Uncertainty in a Heterogeneous Population

Background

Lung cancer screening can reduce cancer mortality. Most implementation studies focus only on low-dose computed tomography (LDCT) and clinical attributes of screening and do not include preferences of potential participants. In this study we evaluated the perceived value of screening programs based on LDCT, breath analysis (BA), or blood biomarkers (BB) according to the perspective of the target population.

Antibiotic prophylaxis in craniotomy: a review

The effectiveness of antibiotic prophylaxis (AP) in craniotomies has been clarified through the accumulation of evidence and increased antibiotic knowledge. This paper focuses on the use of AP in craniotomies during different historical periods and collects highly relevant evidence on this issue. This review surveys different AP guidelines and explains why cefazolin was selected by most guidelines. Recent prominent topics, including strategies to update and implement guidelines and antibiotic efficacy in postoperative meningitis and surveillance and decolonization therapies for methicillin-resistant Staphylococcus aureus, are discussed.     

Inter-Rater Reliability of the PIPES Tool: Validation of a Surgical Capacity Index for Use in Resource-Limited Settings

Introduction

In response to the need for simple, rapid means of quantifying surgical capacity in low resource settings, Surgeons OverSeas (SOS) developed the personnel, infrastructure, procedures, equipment and supplies (PIPES) tool. The present investigation assessed the inter-rater reliability of the PIPES tool.

Methods

As part of a government assessment of surgical services in Santa Cruz, Bolivia, the PIPES tool was translated into Spanish and applied in interviews with physicians at 31 public hospitals. An additional interview was conducted with nurses at a convenience sample of 25 of these hospitals. Physician and nurse responses were then compared to generate an estimate of reliability. For dichotomous survey items, inter-rater reliability between physicians and nurses was assessed using the Cohen’s kappa statistic and percent agreement. The Pearson correlation coefficient was used to assess agreement for continuous items.

Results

Cohen’s kappa was 0.46 for infrastructure, 0.43 for procedures, 0.26 for equipment, and 0 for supplies sections. The median correlation coefficient was 0.91 for continuous items. Correlation was 0.79 for the PIPES index, and ranged from 0.32 to 0.98 for continuous response items.

Conclusions

Reliability of the PIPES tool was moderate for the infrastructure and procedures sections, fair for the equipment section, and poor for supplies section when comparing surgeons’ responses to nurses’ responses—an extremely rigorous test of reliability. These results indicate that the PIPES tool is an effective measure of surgical capacity but that the equipment and supplies sections may need to be revised.     

Comparison of Two Preoperative Inspiratory Muscle Training Programs to Prevent Pulmonary Complications in Patients Undergoing Esophagectomy: A Randomized Controlled Pilot Study

Background

Postoperative pulmonary complications (PPCs) are the most commonly reported complications after esophagectomy. The aim of this study was to examine the effect and feasibility of preoperative inspiratory muscle training-high intensity (IMT-HI), and IMT-endurance (IMT-E) on the incidence of PPCs in patients following esophagectomy for esophageal cancer (EC).

Method

A single-blind, randomized, clinical pilot study was conducted between 2009 and 2012. Forty-five participants were assigned to either IMT-HI or IMT-E. Effectiveness was assessed by analyzing PPCs, length of hospital stay (LOS), duration of mechanical ventilation, stay on the intensive care unit, and number of reintubations. Maximal inspiratory pressure and lung function changes were recorded pre- and post-training. Feasibility was assessed by IMT-related adverse events, training compliance, and patients’ satisfaction.

Results

Thirty-nine patients could be analyzed, 20 patients in the IMT-HI arm and 19 patients in the IMT-E arm. The incidence of PPCs differed significantly between groups and was almost three times lower for the IMT-HI group (4 vs. 11 patients; p = 0.015). Other differences in favor of the IMT-HI group were LOS (13.5 vs. 18 days; p = 0.010) and number of reintubations (0 vs. 4 patients; p = 0.030). Both interventions proved to be equally feasible.

Conclusion

Preoperative IMT-HI showed to be a promising, effective, and feasible intervention to reduce PPCs in EC patients undergoing esophagectomy. Further research with a larger sample size is recommended.     

Short-term dietary adjustment with a hydrolyzed casein-based diet postpones diabetes development in the diabetes-prone BB rat

From earlier studies it appears that weaning associated changes in the animal's physiology and that of the pancreas in particular, render diabetes-prone Bio-Breeding (DP-BB) rats susceptible to the induction and development of insulin-dependent diabetes mellitus (IDDM). In this study we tested whether a short-term dietary adjustment at weaning would influence the development of diabetes later in life. For this purpose a diet in which the protein source was replaced with hydrolyzed casein (HC) was given to the rats from weaning to 60 days of age and from weaning to 130 days of age. The control group received the cereal-based standard diet throughout the experiment. The short-term dietary adjustment resulted in a significant delay of diabetes development. The rats fed the HC diet from weaning to 130 days of age showed a lower incidence of diabetes at 130 days of age. No differences were seen in the histological insulitis scores between the rats of the different treatment groups. Interestingly, when testing (mucosal) immune functions of short-term HC-fed rats, their mesenteric lymph node cells (MLNC) showed increased interferon-gamma (IFN-gamma) and reduced interleukin-10 (IL-10) production after in vitro stimulation. These results demonstrate that short-term dietary adjustments at a young age can influence the course of diabetes later in life. The shift in cytokine profile of MLNC of the HC-fed rats suggests that mechanisms involved can be at the level of both the (mucosal) immune system and the beta cell.     

Increased cholesterol efflux from cultured fibroblasts to plasma from hypertriglyceridemic type 2 diabetic patients: roles of pre beta-HDL, phospholipid transfer protein and cholesterol esterification

We tested whether hypertriglyceridemia associated with type 2 diabetes mellitus is accompanied by alterations in pre beta-HDL, which are considered to be initial acceptors of cell-derived cholesterol, and by changes in the ability of plasma to promote cellular cholesterol efflux. In 28 hypertriglyceridemic and 56 normotriglyceridemic type 2 diabetic patients, and in 56 control subjects, we determined plasma lipids, HDL cholesterol and phospholipids, plasma pre beta-HDL and pre beta-HDL formation, phospholipid transfer protein (PLTP) activity, plasma cholesterol esterification (EST) and cholesteryl ester transfer (CET) and the ability of plasma to stimulate cholesterol efflux out of cultured human fibroblasts. HDL cholesterol and HDL phospholipids were lower, whereas plasma PLTP activity, EST and CET were higher in hypertriglyceridemic diabetic patients than in the other groups. Pre beta-HDL levels and pre beta-HDL formation were unaltered, although the relative amount of pre beta-HDL (expressed as % of total plasma apo A-I) was increased in hypertriglyeridemic diabetic patients. Cellular cholesterol efflux to plasma from hypertriglyceridemic diabetic patients was increased compared to efflux to normotriglyceridemic diabetic and control plasma, but efflux to normotriglyceridemic diabetic and control plasma did not differ. Multiple linear regression analysis demonstrated that cellular cholesterol efflux to plasma was positively and independently related to pre beta-HDL formation, PLTP activity and EST (multiple r=0.48), but not to the diabetic state. In conclusion, cholesterol efflux from fibroblasts to normotriglyceridemic diabetic plasma is unchanged. Efflux to hypertriglyceridemic diabetic plasma is enhanced, in association with increased plasma PLTP activity and cholesterol esterification. Unaltered pre beta-HDL formation in diabetic hypertriglyceridemia, despite low apo A-I, could contribute to maintenance of cholesterol efflux.     

Plasma levels of plasminogen activator inhibitor type 1, beta- thromboglobulin, and fibrinopeptide A before, during, and after treatment of acute myocardial infarction with alteplase

Plasma levels of plasminogen activator inhibitor type-1 (PAI-1), beta- thromboglobulin (beta TG), and fibrinopeptide A (FPA) were followed over 24 hours in 30 patients treated with alteplase for acute myocardial infarction. Samples were taken at baseline (T Oh), after 90 minutes (under alteplase, no heparin, T 1.5h), after 120 minutes (under alteplase and heparin, T 2h), 30 minutes after thrombolytic therapy (T 3.5h), as well as 12 hours (T 12h) and 24 hours (T 24h) after baseline. PAI-1 antigen levels (55 +/- 9 ng/mL at T Oh, mean +/- SEM) decreased to 35 +/- 5 (T 1.5h) and 40 +/- 6 (T 2h) ng/mL under alteplase, before increasing to 84 +/- 22 (T 3.5h), 130 +/- 30 (T 12h), and 64 +/- 7 (T 24h) ng/mL after therapy, P less than .001. A high baseline PAI-1 activity (18 +/- 3 ng/mL) decreased to 2.0 +/- 0.4 (T 1.5h) and 1.7 +/- 0.2 (T 2h) under alteplase and increased to 32 +/- 5 (T 12h) and 19 +/- 3 (T 24h) ng/mL after therapy (P less than .0001). beta TG levels (339 +/- 105 ng/mL at T Oh) decreased to 203 +/- 48 (T 2h), 154 +/- 51 (T 3.5h), 187 +/- 40 (T 12h), and 142 +/- 32 (T 24h) ng/mL under heparin (P less than .01). FPA levels (34 +/- 9 ng/mL at T Oh) increased to 85 +/- 15 ng/mL under alteplase alone (T 1.5h) and normalized under heparin (11 +/- 4, 6 +/- 2, 4 +/- 2, and 3 +/- 1 ng/mL at T 2h, T 3.5h, T 12h, and T 24h, respectively). A high level of FPA at T 3.5h correlated with reocclusion (33 +/- 12 ng/mL, n = 4 v 2.9 +/- 0.5 ng/mL, n = 21, P less than .005). We conclude that plasma levels of PAI- 1 antigen as well as activity markedly increase after alteplase therapy of acute myocardial infarction. The high activity of PAI-1 and decreasing beta TG levels suggest that platelets do not contribute significantly to this phenomenon. The marked increase of FPA levels under recombinant tissue-type plasminogen activator alone and its normalization under heparin emphasize the important role of concomitant anticoagulation in controlling further intravasal fibrin generation under alteplase.     

DLA-identical bone marrow grafts after low-dose total body irradiation: the effect of canine recombinant hematopoietic growth factors

Previous studies found that bone marrow (BM) allografts from DLA- identical littermates resulted in survival of two thirds of recipient dogs after otherwise lethal doses of 450 to 600 cGy of total body irradiation (TBI) because of successful allografts or autologous recovery after rejection of the allografts. The current study asked whether survival could be further improved by treating allograft recipients with recombinant canine granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), or G-CSF/SCF. Of 21 dogs, 14 (67%) receiving allografts but no growth factors survived, 10 with successful allografts (including 5 mixed chimeras) and 4 with autologous recovery; whereas 7 animals died, 5 from infections during BM aplasia and 2 from acute graft-versus-host disease. By comparison, 30 of 34 dogs (88%) receiving hematopoietic growth factors in addition to the BM graft survived, 17 with successful allografts (including 10 mixed chimeras) and 13 with autologous recovery; whereas 4 died, all with infection related to BM aplasia after rejection of the allograft. Survival was similar for recipients of G-CSF, SCF, or the combination of G-CSF and SCF. Logistic regression analyses, which accounted for possible effects of TBI dose, showed a trend for improved survival in dogs receiving growth factors (P = .09), no change in allogeneic engraftment (P = .74), and a slight increase in autologous recovery (P = .22). In agreement with previous data, we found that grafts of BM from DLA-identical littermates improved survival of recipient dogs exposed to low but otherwise lethal doses of TBI. A further improvement in survival could be achieved by additional treatment with G-CSF, SCF, or G-CSF/SCF. Results suggest that treatment by hematopoietic growth factors along with BM grafts should be considered for victims of radiation accidents.     

Establishment and characterization of an Epstein-Barr virus transformed cell line with strong phagocytic activity

An immunoglobulin M (IgM)-positive cell line, Ms 28, apparently spontaneously transformed by Epstein-Barr virus (EBV) was established from peripheral blood cells of a patient with immature myeloblastic leukemia. It has been characterized according to phenotype, cytochemistry, and membrane antigen pattern. The cell line expresses lymphoid markers like CD 19, CD 22, and CD 30 and synthesizes and secretes IgM. Monocyte markers CD 11c, CD 14, and CD 15 are absent. Neither interleukin-1 (IL-1), nor tumor necrosis factor (TNF-alpha) are produced. But Ms 28 cells show strong phagocytic activity and engulf Latex particles and sheep RBCs (SRBCs) that need not to be opsonized. The phagocytic activity can be inhibited by chloroquine. Both phagocytosis and EBV nuclear-antigen (EBNA) expression can be observed in one and the same cell. Ms 28 cells might be useful to study immunologic activities like antigen processing and presentation.